Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections. Academic Article uri icon

Overview

abstract

  • Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most, but not all, patients with autosomal recessive EV. We found that 2 young adult siblings presenting with T cell deficiency and various infectious diseases, including persistent EV-HPV infections, were homozygous for a mutation creating a stop codon in the ras homolog gene family member H (RHOH) gene. RHOH encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients' circulating T cells contained predominantly effector memory T cells, which displayed impaired TCR signaling. Additionally, very few circulating T cells expressed the β7 integrin subunit, which homes T cells to specific tissues. Similarly, Rhoh-null mice exhibited a severe overall T cell defect and abnormally small numbers of circulating β7-positive cells. Expression of the WT, but not of the mutated RHOH, allele in Rhoh-/- hematopoietic stem cells corrected the T cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH deficiency leads to T cell defects and persistent EV-HPV infections, suggesting that T cells play a role in the pathogenesis of chronic EV-HPV infections.

publication date

  • August 1, 2012

Research

keywords

  • Epidermodysplasia Verruciformis
  • T-Lymphocytes
  • Transcription Factors
  • rho GTP-Binding Proteins

Identity

PubMed Central ID

  • PMC3428089

Scopus Document Identifier

  • 84865426636

Digital Object Identifier (DOI)

  • 10.1046/j.0902-4441.2003.00199.x

PubMed ID

  • 22850876

Additional Document Info

volume

  • 122

issue

  • 9